dbSNP rs10872670: AKAP12:p.Lys117Glu (chr6-151348740-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005100.4(AKAP12):c.349A>G(p.Lys117Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.774 in 1,590,998 control chromosomes in the GnomAD database, including 474,860 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.76 ( 42023 hom., cov: 21)

Exomes 𝑓: 0.78 ( 432837 hom. )

Consequence

AKAP12
NM_005100.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.442

Publications

33 publications found

Variant links:

Genes affected

AKAP12 (HGNC:370): (A-kinase anchoring protein 12) The A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins, which have the common function of binding to the regulatory subunit of protein kinase A (PKA) and confining the holoenzyme to discrete locations within the cell. This gene encodes a member of the AKAP family. The encoded protein is expressed in endothelial cells, cultured fibroblasts, and osteosarcoma cells. It associates with protein kinases A and C and phosphatase, and serves as a scaffold protein in signal transduction. This protein and RII PKA colocalize at the cell periphery. This protein is a cell growth-related protein. Antibodies to this protein can be produced by patients with myasthenia gravis. Alternative splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

AKAP12 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.87914E-7).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AKAP12	NM_005100.4 link	c.349A>G	p.Lys117Glu	missense_variant	Exon 4 of 5	ENST00000402676.7	NP_005091.2	Q02952-1Q86TJ9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AKAP12	ENST00000402676.7 link	c.349A>G	p.Lys117Glu	missense_variant	Exon 4 of 5	5	NM_005100.4	ENSP00000384537.2		Q02952-1

Frequencies

GnomAD3 genomes

AF:

0.759

AC:

110917

AN:

146178

Hom.:

41997

Cov.:

show subpopulations

Gnomad AFR

AF:

0.714

Gnomad AMI

AF:

0.631

Gnomad AMR

AF:

0.809

Gnomad ASJ

AF:

0.822

Gnomad EAS

AF:

0.622

Gnomad SAS

AF:

0.659

Gnomad FIN

AF:

0.801

Gnomad MID

AF:

0.797

Gnomad NFE

AF:

0.782

Gnomad OTH

AF:

0.777

GnomAD2 exomes

AF:

0.754

AC:

186973

AN:

248104

AF XY:

0.748

show subpopulations

Gnomad AFR exome

AF:

0.705

Gnomad AMR exome

AF:

0.828

Gnomad ASJ exome

AF:

0.825

Gnomad EAS exome

AF:

0.595

Gnomad FIN exome

AF:

0.787

Gnomad NFE exome

AF:

0.775

Gnomad OTH exome

AF:

0.781

GnomAD4 exome

AF:

0.776

AC:

1121038

AN:

1444722

Hom.:

432837

Cov.:

AF XY:

0.772

AC XY:

555037

AN XY:

718520

show subpopulations

African (AFR)

AF:

0.716

AC:

23436

AN:

32728

American (AMR)

AF:

0.827

AC:

36427

AN:

44036

Ashkenazi Jewish (ASJ)

AF:

0.834

AC:

21427

AN:

25698

East Asian (EAS)

AF:

0.700

AC:

26455

AN:

37790

South Asian (SAS)

AF:

0.657

AC:

56220

AN:

85514

European-Finnish (FIN)

AF:

0.797

AC:

41580

AN:

52190

Middle Eastern (MID)

AF:

0.794

AC:

4506

AN:

5676

European-Non Finnish (NFE)

AF:

0.785

AC:

865080

AN:

1101876

Other (OTH)

AF:

0.775

AC:

45907

AN:

59214

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

11262

22523

33785

45046

56308

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.759

AC:

110995

AN:

146276

Hom.:

42023

Cov.:

AF XY:

0.760

AC XY:

53938

AN XY:

70958

show subpopulations

African (AFR)

AF:

0.715

AC:

27990

AN:

39168

American (AMR)

AF:

0.809

AC:

11624

AN:

14372

Ashkenazi Jewish (ASJ)

AF:

0.822

AC:

2830

AN:

3442

East Asian (EAS)

AF:

0.622

AC:

2954

AN:

4752

South Asian (SAS)

AF:

0.659

AC:

2961

AN:

4490

European-Finnish (FIN)

AF:

0.801

AC:

7811

AN:

9746

Middle Eastern (MID)

AF:

0.800

AC:

224

AN:

280

European-Non Finnish (NFE)

AF:

0.782

AC:

52498

AN:

67154

Other (OTH)

AF:

0.778

AC:

1540

AN:

1980

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1295

2589

3884

5178

6473

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.769

Hom.:

164111

Bravo

AF:

0.752

TwinsUK

AF:

0.780

AC:

2894

ALSPAC

AF:

0.773

AC:

2981

ESP6500AA

AF:

0.698

AC:

3076

ESP6500EA

AF:

0.787

AC:

6767

ExAC

AF:

0.747

AC:

90652

Asia WGS

AF:

0.647

AC:

2249

AN:

3476

EpiCase

AF:

0.780

EpiControl

AF:

0.783

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.7

(source)

DANN

Benign

0.60

DEOGEN2

Benign

0.012

T;T;.;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.16

T;.;T;T

MetaRNN

Benign

7.9e-7

T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-0.46

N;N;.;.

PhyloP100

0.44

PrimateAI

Benign

0.30

PROVEAN

Benign

1.2

N;N;N;N

REVEL

Benign

0.042

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0

B;B;B;B

Vest4

0.015

MPC

0.23

ClinPred

0.0015

GERP RS

2.8

Varity_R

0.032

gMVP

0.015

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs10872670

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over